Zhaoxu Xu1, Haichao Tang1, Tianshu Zhang2, Mingli Sun1, Qiang Han1, Jiao Xu1, Minjie Wei3, Zhaojin Yu4. 1. Department of Pharmacology, School of Pharmacy, China Medical University, No.77, Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China; Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation, China Medical University, No.77, Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China; Liaoning Cancer immune peptide drug Engineering Technology Research Center, China Medical University, No.77, Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China; Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, No.77, Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China. 2. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, No.1 Tian Tan Xi Li, Dongcheng District, Beijing 100050, PR China; No.9, Dongdan Santiao, Dongcheng District, Beijing 100730, PR China. 3. Department of Pharmacology, School of Pharmacy, China Medical University, No.77, Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China; Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation, China Medical University, No.77, Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China; Liaoning Cancer immune peptide drug Engineering Technology Research Center, China Medical University, No.77, Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China; Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, No.77, Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China. Electronic address: weiminjiecmu@163.com. 4. Department of Pharmacology, School of Pharmacy, China Medical University, No.77, Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China; Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation, China Medical University, No.77, Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China; Liaoning Cancer immune peptide drug Engineering Technology Research Center, China Medical University, No.77, Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China; Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, No.77, Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China. Electronic address: yuzhaojin19830813@163.com.
Abstract
AIMS: Testis Expressed 19 (TEX19) is one of cancer/testis antigens identified in recent years and is related to the oncogenesis and progress of several cancers. This study aimed to reveal the role of TEX19 in ovarian cancer (OC) and searched for potential candidate epitope peptides of TEX19 to facilitate clinical application. MAIN METHODS: TEX19 levels were evaluated by immunohistochemistry (IHC) in 98 human ovarian tissue samples. The correlation of TEX19 levels with patients' clinicopathological features was assessed. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were utilized to detect TEX19 levels in ovarian cell lines and TEX19-deficient cells. The level of TEX19 in OVCAR-3 and A2780 was knocked down by small interfering RNA (siRNA), and loss-of-function assays were used to determine the biological effects of TEX19 on the proliferation, migration, and invasion of OC cells. Subsequently, candidate epitope peptides from TEX19 were predicted and verified by the IEDB database, pepsite2 website, MOE software, and T2 cell binding assay. KEY FINDINGS: TEX19 was significantly upregulated in OC which correlated to higher TNM stage, lymph node involvement, and invasiveness. Knockdown of TEX19 inhibited proliferation, migration, and invasion of OC cells. Additionally, we screened four peptides derived from TEX19 and found TL to be the dominant peptide with the greatest affinity with HLA-A*0201. SIGNIFICANCE: Our data indicated a cancer-promoting effect of TEX19 in OC and demonstrated that TL could be a potential candidate for an anti-tumor epitope vaccine of OC, suggesting that TEX19 is a promising biomarker and immunotherapeutic target for OC.
AIMS: Testis Expressed 19 (TEX19) is one of cancer/testis antigens identified in recent years and is related to the oncogenesis and progress of several cancers. This study aimed to reveal the role of TEX19 in ovarian cancer (OC) and searched for potential candidate epitope peptides of TEX19 to facilitate clinical application. MAIN METHODS:TEX19 levels were evaluated by immunohistochemistry (IHC) in 98 humanovarian tissue samples. The correlation of TEX19 levels with patients' clinicopathological features was assessed. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were utilized to detect TEX19 levels in ovarian cell lines and TEX19-deficient cells. The level of TEX19 in OVCAR-3 and A2780 was knocked down by small interfering RNA (siRNA), and loss-of-function assays were used to determine the biological effects of TEX19 on the proliferation, migration, and invasion of OC cells. Subsequently, candidate epitope peptides from TEX19 were predicted and verified by the IEDB database, pepsite2 website, MOE software, and T2 cell binding assay. KEY FINDINGS:TEX19 was significantly upregulated in OC which correlated to higher TNM stage, lymph node involvement, and invasiveness. Knockdown of TEX19 inhibited proliferation, migration, and invasion of OC cells. Additionally, we screened four peptides derived from TEX19 and found TL to be the dominant peptide with the greatest affinity with HLA-A*0201. SIGNIFICANCE: Our data indicated a cancer-promoting effect of TEX19 in OC and demonstrated that TL could be a potential candidate for an anti-tumor epitope vaccine of OC, suggesting that TEX19 is a promising biomarker and immunotherapeutic target for OC.
Authors: Jianhang Zhao; Zhaoxu Xu; Yan Liu; Xiaobin Wang; Xinli Liu; Yanan Gao; Ying Jin Journal: Am J Cancer Res Date: 2022-02-15 Impact factor: 6.166